RegeneRx Biopharmaceuticals Inc. has the long-term goal of developing Thymosin 4 (T24), a naturally occurring peptide, for use in the treatment of ST-elevation myocardial infarction (STEMI). There are no pharmacological agents on the market to prevent cardiac injury and promote repair after a heart attack. T24 has been shown to have a clear positive role in cardioprotection and repair. In heart injury studies in animal models, this peptide reduced damage after ischemic heart injury, protected post-hypoxic cardiac tissue, decreased infarct size, decreased inflammation, promoted angiogenesis, and improved ventricular function and animal survival. In vitro, T24 increased adult and embryonic myocardial and endothelial stem cell migration from explants. These studies demonstrate a strong rationale for use of T24 to prevent cardiac damage post-STEMI and promote regeneration after an infarction, using a safe and well-tolerated pharmacological agent. In order to initiate human clinical trials, RegeneRx completed the development of an injectable formulation of T24 (RGN-352), several nonclinical toxicology studies, and an in vivo safety pharmacology study to support the safety of the drug's first use in man for cardiovascular indications. Recently, RegeneRx successfully completed a double- blind, placebo-controlled, dose-response Phase I safety trial with RGN-352. Several additional nonclinical studies with RGN-352 are required to begin Phase II and Phase III clinical trials. Funding for these FDA-required studies is requested in this grant application. Specifically, this grant requests funding for studies to accomplish the following specific aims related to the safety of T24: (1) pharmacology and repeated-dose toxicity;(2) reproductive toxicology and (3) absorption, pharmacokinetics, distribution, metabolism, and excretion. These are standard tests that will be done by contract research organizations experienced with these types of studies. RGN-352 has the potential to improve damaged heart tissue after myocardial infarction, thus, reducing short- and long-term complications, such as heart failure and life-threatening arrhythmias. Reducing these complications in STEMI patients in the U.S. would not only significantly improve quality-of-life, but also would greatly reduce long-term health care costs over their lifetimes. PUBLIC HEALTH RELEVANCE: The greatest risk to a patient suffering an acute, severe heart attack is permanent damage to the heart tissue through oxygen depletion caused by the blood clot to a major heart vessel. Currently there are no drugs on the market that reduce heart damage or repair heart tissue after an acute, severe heart attack. This project furthers the development and commercialization of a drug that has the potential to reduce damage and even to repair heart tissue during and after such an event.